Dual effect of cholesterol on interfacial water dynamics in lipid membranes: Interplay between membrane packing and hydration

TL;DR

This study uses molecular dynamics simulations to reveal how cholesterol modulates interfacial water dynamics in lipid membranes, showing a complex interplay between membrane packing and hydration that affects water mobility.

Contribution

It uncovers the nonmonotonic effects of cholesterol on interfacial water dynamics and elucidates the underlying mechanisms involving membrane packing and hydration changes.

Findings

Cholesterol causes a transient slowdown of water dynamics at 303 K in ripple phase.

Higher Chol concentrations accelerate water dynamics across temperatures.

Hydrogen bond lifetime decreases with increasing Chol, indicating altered water-membrane interactions.

Abstract

Water contained within biological membranes plays a critical role in maintaining the separation between intracellular and extracellular environments and facilitating biochemical processes. Variations in membrane composition and temperature lead to phase state changes in lipid membranes, which in turn influence the structure and dynamics of the associated interfacial water. In this study, molecular dynamics simulations were performed on binary membranes composed of dipalmitoylphosphatidylcholine (DPPC) or palmitoyl sphingomyelin (PSM) mixed with cholesterol (Chol). To elucidate the effects of Chol on interfacial water, we examined the orientation and hydrogen-bonding behavior of water molecules spanning from the membrane interior to the interface. As the Chol concentration increased, a transient slow down in water dynamics was observed in the ripple phase at 303 K. Conversely, at higher Chol concentrations, water dynamics were accelerated relative to pure lipid membranes across all temperatures studied. Specifically, at a Chol concentration of 50%, the hydrogen bond lifetime in DPPC membranes decreased to approximately 0.5-0.7 times that of pure lipid membranes. This nonmonotonic behavior is attributed to the combined effects of membrane packing induced by Chol and a reduced density of lipid molecules in the hydrophilic region, offering key insights for modulating the dynamical properties of interfacial water.